All references to patent applications, issued patents, articles, trade journals and manuals are expressly intended to incorporate such materials expressly herein in their entirety as if set forth specifically herein. The above listed materials are only provided as examples and should not be regarded as limiting to the type of materials expressly incorporated herein.
1. Field of the Invention
The presently claimed and disclosed inventions relate, in general, to methods of radiation dosimetry and imaging using scintillation luminescence. More particularly, materials having a scintillation luminescence response to radiation that varies with total radiation dose received can be used for dosimetry monitoring, including, but not limited to nanoparticles for in vivo, real-time dosimetry. Energy-transfer nanocomposite materials as well as methods of making and using such materials in various applications including, but not limited to, in vivo radiation dosimetry and imaging, are disclosed. More particularly, the presently claimed and disclosed inventions relate to nanoparticle scintillation luminescence particles encapsulated in hosts of the general formula BaFX and BaFX:Eu2+ where X=Cl, Br and I.
2. Background
In the presently disclosed invention, special characteristics of materials are used to generate scintillation luminescence (SL), meaning the emission of light (UV, visible, near IR, or IR wavelengths) in response to radiation. SL is also known in the art as X-ray luminescence, although other forms of radiation such as gamma ray, alphas, betas, neutrons, pi-mesons, ions (carbon and neon) and positrons can also cause SL.
When X-rays are used for imaging (for example, medical or security or non-destructive evaluation), the detection of the X-rays is done by several methods. For example, the use of a film is very common, sometimes in conjunction with a scintillator to convert the X-rays to visible light. Scintillators are also used with CCD cameras (charge-coupled device) for the digital acquisition of images. In general, a scintillator must emit in a suitable wavelength range, have high efficiency, have high sensitivity, have a fast response and exhibit high transparency to the emitted light. Although there are many scintillator materials available, no one single scintillator provides the desired combination of stopping power (absorption coefficient), light output and decay time for every application.
The strong luminescence and ultra-fast decay lifetime of semiconductor nanoparticles have suggested that these types of materials may provide a new solution for the design and fabrication of high efficiency scintillators having rapid response rates. However, the stopping power of most semiconductors is low and their scintillation luminescence is very weak. By encapsulating semiconductor nanoparticles with materials with high stopping power and that transfer energy efficiently to the semiconductor nanoparticles (such as BaFX where X=Cl, Br, I), as in the presently disclosed and claimed invention, a new type of scintillator has been developed that has efficient emission, a fast response, and a selectable wavelength of emission. Additionally, with regard to the extensive use of X-ray and similar radiation technologies in the medical industry, manufacturing, security, inspection, non-destructive testing, and other applications, the use of nanocomposite materials holds the potential for higher resolution imaging at lower energy levels, resulting in substantial reductions in cost, complexity, hazards, and other negative aspects of the use of these processes.
Thus, it is presently disclosed and claimed that SL can be used in biomedical applications such as in vivo dosimetry and radiation dose imaging. In one aspect of the presently disclosed and claimed inventions, nanoparticles or bulk materials that emit SL upon exposure to radiation such as X-rays are injected into tumors with two possible outcomes. First, if the SL is stable and proportional to the radiation dose rate, then by measuring and integrating the amount of emission from these nanoparticles, the total X-ray dosage sustained by the tumor can be assessed, thus allowing the nanoparticles to serve as a real-time dosimeter. Second and more particularly, for materials in which the wavelength or intensity of one or more peaks in the SL change with radiation dose, those changes can be monitored to determine the dose.
In vivo radiation detection has additional requirements as well as strong scintillation luminescence. In vivo injection requires high solubility, stability in solution, little to no toxicity, biocompatibility, and no leakage within a biological environment. Additionally, the emission wavelengths are preferably detectable through tissues, requiring emission in a range from 700-1200 nm. These requirements are met by the use of nanoparticle SL for in vivo dosimetry, X-ray (and other energy source) imaging, radiation therapy dose control, and other applications.